Sivan J, Degen AA, Horesh SJA
… +4 more, Tesler I, Hadad S, Boni H, Kam M
Gen Comp Endocrinol
· 2025 Aug · PMID 40582515
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Testosterone levels have been linked to reproduction and locomotor activities in vertebrates and even to some invertebrates. However, the relationship between testosterone concentration and daily distance travelled (DDT)...Testosterone levels have been linked to reproduction and locomotor activities in vertebrates and even to some invertebrates. However, the relationship between testosterone concentration and daily distance travelled (DDT) in a free-ranging reptile has not been tested. The aim of this study was to fill this gap. Seasonal plasma testosterone concentration in the free-ranging male Saharan sand viper, Cerastes vipera, was reported to be bimodal: a large peak in spring during spermatogenesis and mating, and a small peak in autumn, during spermatogenesis but without mating prior to hibernation. We hypothesized that DDT would be bimodal as well, the pattern coinciding with testosterone concentration. To test this hypothesis, we measured monthly DDT in free-ranging C. vipera of the same population at the same site, and compared the pattern with that of plasma testosterone concentrations reported earlier. A bimodal pattern in DDT was observed that coincided with testosterone concentration, and, therefore, our hypothesis was supported. This is the first study demonstrating a link between plasma testosterone concentration and DDT in a free-ranging animal; however, the link is correlational as there was no manipulation and cannot be attributed to a casual effect. Further studies are warranted to clarify the relationship between testosterone level and DDT.
Surber-Cunningham LL, Jimenez LS, Mobo LW
… +2 more, Westrick SE, Fischer EK
Gen Comp Endocrinol
· 2025 Aug · PMID 40581054
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In vertebrates, the glucocorticoid "stress" response (corticosterone or cortisol) through the hypothalamic-pituitary-adrenal (HPA) axis influences many essential functions, including behavior, metabolism, immunity, and o...In vertebrates, the glucocorticoid "stress" response (corticosterone or cortisol) through the hypothalamic-pituitary-adrenal (HPA) axis influences many essential functions, including behavior, metabolism, immunity, and ontogenetic transitions. During development, stress responses can be adaptive if they facilitate antipredator behavior and modulate developmental speed to adjust to environmental conditions; however, these same responses can be maladaptive when energetic costs become too high and developmental speed trades-off with size and health at maturity. Thus, the timing of HPA-axis development may be aligned with specific developmental challenges and opportunities presented by a species' life history strategy. In anurans (frogs and toads), corticosterone plays critical roles in development and behavior, and concentrations can fluctuate in response to environmental stressors. Given the role of corticosterone in ontogenetic changes and behaviors, we studied the development of the glucocorticoid stress response in tadpoles of the dyeing poison frog (Dendrobates tinctorius), a species with a unique life history that includes transport to water after hatching on land and aggressive and cannibalistic behavior. We measured the excretion rate and whole-body concentration of corticosterone and the corticosterone response to adrenocorticotropic hormone (ACTH) in free-swimming tadpoles after transport and throughout metamorphosis. We found no significant differences across development in excretion rates or whole-body concentration of corticosterone, nor corticosterone response to ACTH, indicating that that the glucocorticoid response develops early in ontogeny. This pattern differs from those in other species, suggesting the unique ecological pressures faced by D. tinctorius have shaped the development of the glucocorticoid stress response in this species. More broadly, this study illustrates how life history strategies and tradeoffs impact the timing of the development of stress responsivity.
Chivite-Alcalde M, Culbert BM, Larson-Hossack S
… +2 more, Míguez JM, Bernier NJ
Gen Comp Endocrinol
· 2025 Aug · PMID 40581053
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Ammonia is neurotoxic and exposure to high environmental ammonia (HEA) activates the hypothalamic-pituitary-interrenal (HPI) axis in teleosts. To gain insight into the neural factors that regulate the HPI axis in respons...Ammonia is neurotoxic and exposure to high environmental ammonia (HEA) activates the hypothalamic-pituitary-interrenal (HPI) axis in teleosts. To gain insight into the neural factors that regulate the HPI axis in response to this environmental stressor, as well as elucidate potential interactions between these factors, we exposed rainbow trout to one of three ammonia levels (0, 650, 1000 μM NHCl) for 24 or 96 h and assessed the gene expression and circulating levels of key determinants of HPI axis activity. In parallel with circulating ammonia concentrations, plasma cortisol levels increased dose-dependently after 24 h of HEA exposure and partially recovered after 96 h. HEA exposure also elicited dose-, time-, and brain region-specific changes in components of the central serotonergic (5-HTergic; tph2, htr1aa, htr1b, htr2c), corticotropin-releasing factor (crfb), arginine vasotocin (avt, avtr1a, avtr2), and isotocin (it, itr) signaling systems. Moreover, while intraperitoneal injections of 5-HT and 5-HT receptor antagonists reduced basal cortisol levels, treatment with 5-HT and 5-HT receptor antagonists blocked the increase in plasma cortisol elicited by HEA. Finally, treatment with specific 5-HT receptor antagonists blunted the HEA-induced increases in brain preoptic area crfb, avt, and it expression. These findings implicate 5-HT and multiple peptidergic systems in the hypophysiotropic regulation of the HPI axis in response to HEA exposure and provide novel insight into the multifactorial neural circuitry mediating the neuroendocrine stress response in fishes.
Gen Comp Endocrinol
· 2025 Aug · PMID 40543819
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The role of neuropeptide Y (NPY) in regulating ovarian functions has primarily been studied in mammals, while it remains meagrely explored in non-mammalian vertebrates. Our study is the first to report ovarian expression...The role of neuropeptide Y (NPY) in regulating ovarian functions has primarily been studied in mammals, while it remains meagrely explored in non-mammalian vertebrates. Our study is the first to report ovarian expression of npy and its receptor, npyr, in a reptile, Hemidactylus flaviviridis. Quantitative real-time PCR analysis demonstrated high expression of npy/npyr during early and late recrudescence, while significantly low levels were noted during regression. The study also examined role of NPY in modulating lizard ovarian functions, wherein in vitro treatment of recrudescent ovaries with NPY increased the mRNA expression of anti-apoptotic gene B-cell lymphoma 2 (bcl 2), and suppressed pro-apoptotic gene cysteine-aspartic acid protease-3 (caspase 3). NPY also stimulated cell proliferation/differentiation markers; stem cell factor (scf), receptor tyrosine kinase (c-kit), proliferating cell nuclear antigen (pcna), growth differentiation factor-9 (gdf-9), bone morphogenetic protein-15 (bmp-15), as well as gonadotropin and sex steroid receptors, follicle stimulating hormone receptor (fshr), estrogen receptor α, β (er-α, er-β), and progesterone receptor (pr). Also, NPY influenced ovarian steroidogenesis by upregulating steroidogenic acute regulatory protein (star) and cytochrome P450a family 19 (cyp19) mRNA expression. However, steroid estimation by ELISA indicates NPY-mediated differential modulation of steroidogenesis as progesterone production was elevated, while estradiol production was inhibited. Further, ovarian npy/npyr was differentially regulated by gonadotropin, sex steroids, neuropeptides, and adipokines. Expression of ligand and receptor was stimulated by 5α-dihydrotestosterone (DHT), 17β-estradiol (E), kisspeptin, leptin, and nesfatin-1 but inhibited by follicle stimulating hormone (FSH) and substance P. Taken together, present study provides a comprehensive picture of ovarian npy/npyr in wall lizard.
Assisted reproductive technologies are important for protecting threatened amphibian species globally. These technologies can overcome amphibian breeding failure and improve threatened species management and research qua...Assisted reproductive technologies are important for protecting threatened amphibian species globally. These technologies can overcome amphibian breeding failure and improve threatened species management and research quality in the fields of reproductive biology and ecology. One assisted reproductive technology is inducing spermiation using exogenous hormone injections. However, the impacts of repeatedly administering exogenous hormones on sperm quality and quantity remain poorly understood. In this study we repeatedly administered an exogenous hormone - human chorionic gonadotropin - in the threatened Australian frog species, Litoria aurea. We analysed sperm quantity and quality over 3-4 hormonal administrations at biweekly, weekly, and fortnightly frequencies (n = 6 for each group). Sperm quality and quantity were assessed at three timepoints over a 6-hour period following each hormonal administration (hours 2, 4, and 6 post-injection). We found that repeated administrations significantly reduced sperm quantity and quality via reduced concentration, volume, total sperm counts, and viability. With repeated administrations, the timing of sperm release varied: after only one administration, sperm was released equivalently in hours 2, 4 and 6 post-injection, whereas after several administrations, sperm release was delayed such that 6 hr post-injection produced higher quantity and quality sperm. Overall, our results demonstrate that repeated hormonal administration of male L. aurea reduces sperm quantity and quality, and individuals will need substantial time to regenerate sperm between administrations.
Adrenarche, or the postnatal activation of the adrenal gland, is a phenomenon exclusive to some primates that is evidenced by high levels of the hormones dehydroepiandrosterone (DHEA) and its sulfated form (DHEAS), indep...Adrenarche, or the postnatal activation of the adrenal gland, is a phenomenon exclusive to some primates that is evidenced by high levels of the hormones dehydroepiandrosterone (DHEA) and its sulfated form (DHEAS), independent of the onset of puberty. Within primates, two patterns of adrenal secretions occur: a prepubertal increase in DHEAS levels (adrenarche) that has been reported in humans and great apes, and a continuous postnatal decline on DHEAS levels with age, observed in cercopithecines (e.g., macaques and baboons). Our research seeks to determine the pattern of DHEAS secretion during hylobatid development. DHEAS was measured by enzyme immunoassay in cross-sectional fecal samples from 35 female and 29 male zoo-housed hylobatids (Hylobates, Nomascus, Symphalangus) ranging from age 1 to 54 years. Additionally, we measured longitudinal fecal samples from 7 female hylobatids under human care (6 Nomascus, 1 Hoolock). Our study tested the effects of age, sex, and genus on fecal DHEAS levels using generalized linear mixed-effects models. The models were separated by genus and showed that age was positively correlated with a prepubertal increase in fecal DHEAS across all genera, indicating that the hylobatids exhibit delayed adrenarche. A significant effect of sex was only identified in the Symphalangus model. Results from adult and old hylobatids did not exhibit decreasing DHEAS associated with adrenal senescence, which is characteristic of humans and other primates. The evidence of a delayed DHEAS increase observed across all hylobatid genera suggests a shared developmental characteristic among all ape species.
Asprosin regulates various aspects of physiology in mammals including reproduction. It is reported to profoundly affect both male and female reproductive functions including gametogenesis and steroidogenesis. Asprosin is...Asprosin regulates various aspects of physiology in mammals including reproduction. It is reported to profoundly affect both male and female reproductive functions including gametogenesis and steroidogenesis. Asprosin is the cleaved product of a profibrillin protein encoded by the fbn1 gene. For the first time in non-mammalian vertebrates, our group demonstrated the ubiquitous expression of fbn1 and characterized asprosin protein in silico in teleost Channa punctata commonly known as spotted snakehead (ss). Based on the prominent expression of the fbn1 gene and the reproductive phase-dependent temporal expression of fbn1 in the ovary of C. punctata, we hypothesized the regulatory role of asprosin in female reproduction similar to that reported in mammals. In vitro studies confirmed the effect of asprosin on the oogenesis and steroidogenesis in C. punctata. Asprosin significantly enhanced the expression of genes crucial for oogenesis such as pcna and gdf9. It also increased the transcription of gonadotropin receptors and sex steroid receptor genes. In addition to this, asprosin accentuated the expression of steroidogenic markers such as star and cyp17a1 along with 17α, 20β dihydroxy-progesterone levels. We also measured the levels of the second messenger cAMP in ovaries exposed to asprosin to explore the probability of GPCRs as asprosin receptors. However, asprosin could not alter the cAMP levels indicating that, in the ovary of teleosts, receptors other than GPCRs might be involved in transducing asprosin action. Thus, the present study in elucidates the important role of asprosin in modulating the ovarian functions in C. punctata.
Climate change is altering the frequency and intensity of environmental extremes, and the diurnal rates of environmental change. The daily reaction norms of wild animals show spatial and temporal plasticity to allow appr...Climate change is altering the frequency and intensity of environmental extremes, and the diurnal rates of environmental change. The daily reaction norms of wild animals show spatial and temporal plasticity to allow appropriate physiological responses to predictable environmental challenges, but these responses have rarely been quantified in wild birds. We addressed this by determining whether physiological stress indices (corticosterone [CORT], glucose [GLU], and circulating heat shock proteins [Hsp]) vary with ambient temperature (T) or time of day across a 6 latitudinal gradient (32-38 S). We sampled house sparrows, Passer domesticus, at three locations with varying daily rates of T increases in 2015 and in 2019-2020 to determine whether physiological responses to capture and handling stress change diurnally. As predicted, plasma CORT and GLU increased during stress. Baseline CORT and GLU levels did not change during the day, but the amplitude of plasma CORT increase (delta CORT) in response to capture decreased as T increased, as was the case for GLU, in birds with initially high baseline CORT. Neither baseline nor stress-related plasma CORT or GLU differed consistently across sampling locations. Heat-shock cognate 70 (Hsc70) and heat-shock protein 90α (Hsp90) showed clear temporal dynamics across the day. Thus, the reaction norms of heat shock proteins are temporally plastic during the day and in response to daily T changes, as are the reaction norms of CORT and GLU in response to acute stress. However, the study provides little evidence for such plasticity in reaction norms as a function of average local thermal conditions.
Vasopressin (VP) and its non-mammalian homolog vasotocin (VT) are secreted from the posterior pituitary to control various physiological phenomena via G protein-coupled receptors. The six known subtypes of VP/VT receptor...Vasopressin (VP) and its non-mammalian homolog vasotocin (VT) are secreted from the posterior pituitary to control various physiological phenomena via G protein-coupled receptors. The six known subtypes of VP/VT receptor family (V1a/bR and V2a/b/c/dR) originate from a single ancestral molecule, that most likely coupled with Gα and used Ca for signaling. However, among the current VP/VT receptors, V2aR predominantly couples with Gα and increases intracellular cAMP levels. This receptor is also known to mediate the potent antidiuretic effect of VP/VT, and therefore is clinically important. Although the structure-function relationship of V2R has been of great interest to researchers, an evolutionary perspective was missing; how did the ancestral V2aR switched its G protein selectivity? To address this question, a comparative study between V2aR and its Ca-signaling cognates (V2b/c/dR) is needed. The aim of the present study was to identify residues/motifs that are crucial to cAMP signaling by V2aR; chimeric receptors were engineered using the functional V2aR and V2bR of medaka. In vitro assays demonstrated that Gα-coupling ability of the receptors can be altered by swapping a single residue in the second intracellular loop (ICL2), without affecting Gα-coupling ability. The three-dimensional models predicted in silico suggested that the interaction between ICL2 and Gα-αN chain and Gα-β2/β3 loop contributes to the stabilization of the signaling complex, enhancing the receptor's capacity to stimulate cAMP pathway upon ligand binding. These findings provide new insights into the molecular and functional evolution of V2aR, as well as into the mechanisms of G protein selectivity of GPCR.
The appetite in fish is a multifaceted phenomenon that comprises specialized interactions between brain and peripheral signals, and as a result, appetite is either stimulated or inhibited. Cholecystokinin (Cck) and gastr...The appetite in fish is a multifaceted phenomenon that comprises specialized interactions between brain and peripheral signals, and as a result, appetite is either stimulated or inhibited. Cholecystokinin (Cck) and gastrin-releasing peptide (Grp) are two postprandially released gastrointestinal peptide hormones that affect feed intake in fish. As the stimulatory or inhibitory effects of hormones can vary in duration and strength, making the nature of hormone effects dynamic, we modelled the dynamics of Cck and Grp using a direct, non-stressful approach. Fish were hormonally treated through an intraperitoneal cannula and feed intake was monitored for 12 h post-injection using a self-feeder system. Cck and Grp decreased feed intake in a dose-dependent manner, hormone-specific both in terms of magnitude and duration. Cck had an immediate inhibitory effect on feed intake, which lasted two-three hours, whereas the immediate inhibitory effect of Grp lasted for the entire 12-hour observation period. The data suggest that Cck acts as a short-term satiety signal in rainbow trout, while Grp acts as a longer-term appetite suppressor.
Silva SC, Correia TM, Manchado M
… +1 more, Power DM
Gen Comp Endocrinol
· 2025 Jun · PMID 40456456
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The thyroid hormones (THs) are proposed as putative regulators of immune system maturation in developing teleost fish. To gain insight into this process the Senegalese sole (Solea senegalensis) that has a well-characteri...The thyroid hormones (THs) are proposed as putative regulators of immune system maturation in developing teleost fish. To gain insight into this process the Senegalese sole (Solea senegalensis) that has a well-characterized TH-driven metamorphosis was used. Differential gene expression analysis was performed across developmental stages (n = 3 per stage): pre-metamorphosis, onset of metamorphosis, metamorphosis, early climax, climax, and post-metamorphic juveniles. Metamorphosis is a massive gene-oriented developmental process, involving the differential expression of 8145 genes. Clustering analysis was used to identify immune-related genes with similar expression patterns to hypothalamus-pituitary-thyroid (HPT) axis-related genes. TH-regulated candidate immune genes were identified (133) and analysis of their promoter region revealed 84 contained putative TH receptor (TR) binding sites (TREs). Two consensus TRE sequences were identified in the candidate genes, 5'-ntgnGntCacan (exclusive to TRα), and 5'-nnntGgtCannn (common to both TRs). TRα-exclusive TREs were less common than those that bound interchangeably TRα and TRβ. In the promoter region, TRα-exclusive TREs were always accompanied by the pan-TRE consensus sequence, never occurring independently.
Hashmi WJ, Turner MM, Max-Harry IM
… +9 more, Hoggard NK, Fischbach AH, Yuan S, Davis E, Kantake N, Kopchick JJ, Hildreth BE, Toribio RE, Rosol TJ
Gen Comp Endocrinol
· 2025 Jun · PMID 40451546
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Parathyroid hormone-related protein (PTHrP) is a polyhormone consisting of an N-terminus, a mid-region, a nuclear localization sequence (NLS), and a C-terminus. The NLS and C-terminus of PTHrP regulate endochondral bone...Parathyroid hormone-related protein (PTHrP) is a polyhormone consisting of an N-terminus, a mid-region, a nuclear localization sequence (NLS), and a C-terminus. The NLS and C-terminus of PTHrP regulate endochondral bone formation, craniofacial development, hematopoiesis, and survival. Our laboratory has developed Pthrp Δ/Δ mice lacking the NLS and C-terminus of PTHrP, which exhibit severe growth delay and early mortality within the first week of life. This study investigates the growth hormone (GH)-IGF-1 axis in Pthrp Δ/Δ mice. PTHrP is expressed by various endocrine cells, including pituitary endocrine epithelial cells of the adenohypophysis. Histopathological, biochemical, ultrastructural, and gene expression analyses were performed on the pituitary from Pthrp Δ/Δ and age-matched control mice. Pituitary glands from Pthrp Δ/Δ mice had normal cellularity; however, the pituitary somatotrophs had increased Gh mRNA expression with a decrease in the number and size of cytoplasmic secretory granules containing GH. Plasma GH concentrations were either normal or increased, and plasma ACTH concentrations were increased. Western blot analysis of the pituitary glands revealed reduced GH in Pthrp Δ/Δ mice. The plasma concentrations of IGF-1 and liver Igf1 mRNA expression and glycogen content were decreased in Pthrp Δ/Δ mice. Western blot analysis of liver from Pthrp Δ/Δ mice showed a significant reduction in both total and phosphorylated Janus Kinase 2 (JAK2) proteins and total and tyrosine-phosphorylated STAT5b proteins compared to controls. In conclusion, the lack of the NLS and C-terminus of PTHrP disrupted the normal GH-IGF-1 axis, leading to impaired IGF-1 production by the liver.
Gen Comp Endocrinol
· 2025 Jun · PMID 40446858
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Vertebrate sex determination is remarkably diverse. In species with genetic sex determination, reproductive physiology and sex-specific behaviour are influenced by sex chromosomes and sex steroid hormones. However, some...Vertebrate sex determination is remarkably diverse. In species with genetic sex determination, reproductive physiology and sex-specific behaviour are influenced by sex chromosomes and sex steroid hormones. However, some species experience sex reversal where the influence of sex chromosomes on sexual development is modulated by mutations or environmental conditions, leading to animals that phenotypically mismatch with their genotype. In these species, sex-reversed ('discordant') individuals can theoretically exhibit traits that are similar to either their phenotypic or genotypic sex. In the central bearded dragon (Pogona vitticeps), high incubation temperatures produce sex-reversed females with male-type sex chromosomes (ZZf). ZZf display a mix of male-like and intermediate traits compared to males (ZZm) and concordant females (ZWf). Sex steroid profiles could drive these differences but are yet to be examined in P. vitticeps. We measured testosterone (T) and estradiol (E2) in ZWf, ZZf, and ZZm dragons at three timepoints across a breeding season. As sex steroids can potentially affect offspring if maternal hormones are transmitted to eggs, we also compared T and E2 levels in egg yolks from ZZf and ZWf females. Sex-reversed ZZf had lower T levels than males and similar T and E2 levels to ZWf across the breeding season. ZWf and ZZf laid eggs with similar levels of T and E2. We found a negative association between maternal and yolk E2 levels, but no association between maternal and yolk T. Our results show that sex steroid profiles in sex-reversed ZZ female P. vitticeps reflect phenotypic, not genotypic sex, suggesting circulating sex steroids do not drive trait differences between discordant and concordant females.
Hébert M, Ihalainen E, Edwards SC
… +2 more, Meddle SL, Healy SD
Gen Comp Endocrinol
· 2025 Jun · PMID 40412667
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Despite its fundamental importance for avian reproduction, the hormonal mechanisms supporting nest building remain poorly understood. While nest building by both male and female builders requires circulating sex steroids...Despite its fundamental importance for avian reproduction, the hormonal mechanisms supporting nest building remain poorly understood. While nest building by both male and female builders requires circulating sex steroids, it is not clear whether these steroids are required throughout building. We, therefore, sought to determine circulating testosterone dynamics in male zebra finches during early breeding, specifically focusing on the nest building period. We collected plasma samples from two cohorts of birds at three of the following four timepoints: before (baseline), following pairing, during, and after nest building. To dissociate the end of nest building from incubation onset we daily removed any eggs laid and terminated nest building once we had sampled males during nest building. Male circulating testosterone levels remained stable following pairing with a female and throughout nest building. However, testosterone titers dropped once nest building had stopped. We also found evidence to suggest that, following pairing with a female, circulating testosterone titers can predict a male's future readiness to build. Together, our data suggest that circulating testosterone is important throughout nest building, not decreasing until the end of nest building activities, perhaps through a 'self-feedback' mechanism.
Yasmin F, Sutradhar S, Roy A
… +1 more, Mukherjee S
Gen Comp Endocrinol
· 2025 Jun · PMID 40388990
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The dietary protein and tryptophan of fish feed have vital roles in the growth performance, stress management, and digestive physiology of fish. However, in this context, the functions of gut melatonin, which depend on t...The dietary protein and tryptophan of fish feed have vital roles in the growth performance, stress management, and digestive physiology of fish. However, in this context, the functions of gut melatonin, which depend on the availability of food, the timing of food supply, the frequency of feeds/day, the quality of food, and the growth stages of carp, still need to be clarified. Hence, the present study aimed to investigate the impact of dietary quality on specific growth rate (SGR), residual gut content (RGC), feeding intensity (FI), gut melatonin, gut oxidative stress and its major antioxidants, vital digestive enzymes in juvenile carp, Catla catla (mean body weight: 274 ± 16.63 g). Besides, serum melatonin and ovarian melatonin, gonado-somatic index (GSI), and different growth stages of oocytes were also assessed before the estimation of oxidative stress and major antioxidant enzymes in the ovary. The fish were fed four diets viz. (i) a standard diet (SD/control) (with 34.99 % protein, 14.56 % carbohydrate, 9.84 % oil, and 0.36 % L-tryptophan) (ii) one protein (PRD with 41.02 % protein and 0.46 % L-tryptophan), (iii) two L-tryptophan (TrpRD1 with 0.96 %, and TrpRD2 with 1.36 % tryptophan), -rich diets for 30 days. The SGR was higher only in PRD, but feeding was reduced in PRD and TrpRDs compared to SD-fed carp. However, the PRD and TrpRDs stimulated gut melatonin, digestive enzymes and all the studied antioxidants with reduced oxidative stress by lowering malondialdehyde (MDA). Moreover, a parallel increase in serum melatonin and ovarian melatonin with gut melatonin has been noticed in both the PRD and TrpRDs. All these experimental diets showed pro-gonadal effects by increasing stage-I oocytes and by reducing oxidative stress in the developing ovary in juvenile carp, compared to SD-fed carp. This opens avenues for future research on the role of feed-induced gut melatonin in fish nutrition and reproduction.
Chepurny OG, Liles AN, Cham N
… +6 more, Matsoukas MT, Liapakis G, Meng Q, Cooney RN, Doyle RP, Holz GG
Gen Comp Endocrinol
· 2025 Jun · PMID 40347985
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Chimeric peptides comprised of amino acid sequence motifs found within hormones, neuropeptides, and insect or lizard toxins are now under investigation for their potential use in therapeutics. Here, we report the discove...Chimeric peptides comprised of amino acid sequence motifs found within hormones, neuropeptides, and insect or lizard toxins are now under investigation for their potential use in therapeutics. Here, we report the discovery of one such peptide designated as Black Widow Spider-Exendin-4 (BW-Ex-4). It consists of a putative G protein-coupled receptor (GPCR) binding domain present within αLatrotoxin (αLTX) isolated from Latrodectus, and fused to N- and C- terminal motifs found within the glucagon-like peptide-1 receptor (GLP-1R) agonist Exendin-4 isolated from Heloderma. FRET reporter assays that monitor cAMP production establish BW-Ex-4 to be a specific GLP-1R agonist without any stimulatory action at glucose-dependent insulinotropic peptide (GIP), glucagon, or corticotropin releasing hormone (CRH) receptors. Structural modeling studies of the predicted BW-Ex-4 binding sites at GPCRs of Family B provide new insights concerning the molecular basis for chimeric peptide stimulatory actions at the GLP-1R. We also report that BW-Ex-4 acts in obese hyperglycemic Lepr mice to suppress appetite, lower body weight, improve glucoregulation, and to reduce circulating levels of pro-inflammatory cytokines. Collectively, these findings establish a combinatorial chimeric peptide chemistry in which αLTX serves as a molecular scaffold for the design of hybrid peptides with novel GPCR stimulating properties.
Gen Comp Endocrinol
· 2025 Jun · PMID 40268205
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Neuropeptide FF (NPFF) is one of the members of RF-amide peptide family, which has been implicated in diverse physiological processes across mammals. However, there is scarce information regarding the biological function...Neuropeptide FF (NPFF) is one of the members of RF-amide peptide family, which has been implicated in diverse physiological processes across mammals. However, there is scarce information regarding the biological function of NPFF in fish reproduction. In the current study, npff was identified and characterized in the half-smooth tongue sole. The NPFF precursor consisted of one signal peptide and two mature peptides, designated as NPFF and NPAF. Analysis of tissue distribution indicated that npff exhibited high expression levels in the brain and pituitary, while its mRNA levels were much lower in other peripheral tissues. Subsequently, the possible function of NPFF and NPAF on the brain-pituitary-gonad reproductive axis was studied in this species by intraperitoneal injection. At the brain level, both NPFF and NPAF had an inhibitory influence on the levels of transcripts corresponding to kiss1, kiss1r, kiss2, gnrh3, spx1, pnx, gpr173a, and gpr173b. NPFF reduced gnrh2 mRNA levels, but promoted gnihr expression. Moreover, NPAF down-regulated gnih and tac3 expression. At the pituitary levels, gh, gthα, and fshβ mRNA levels were suppressed by NPFF and NPAF, whereas lhβ mRNA levels were elevated. In the ovary, these two peptides stimulated expression of star, p450c17, and fshr. Likewise, NPFF increased 17β-hsd and lhr mRNA levels, and NPAF stimulated p450arom transcript levels. However, 3β-hsd was inhibited by NPFF. Overall, our results suggest that NPFF and NPAF may play distinct roles in control of reproduction of half-smooth tongue sole at multiple levels of the brain-pituitary-ovarian axis.
Gen Comp Endocrinol
· 2025 Jun · PMID 40254037
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The vertebrate reproductive system is controlled by the brain-pituitary-gonadal reproductive endocrine axis (BPG axis). Gonadotropin-releasing hormone (GnRH) secreted from the hypothalamus regulates the secretion of two...The vertebrate reproductive system is controlled by the brain-pituitary-gonadal reproductive endocrine axis (BPG axis). Gonadotropin-releasing hormone (GnRH) secreted from the hypothalamus regulates the secretion of two gonadotropic hormones (GTHs), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), in the pituitary gland. Steroid hormones, such as androgens and estrogens, secreted in response to GTH stimulation, regulate the development of male and female gametes. Recently, various neuropeptides have been identified in mammals as factors that regulate the BPG axis from the upstream, demonstrating their importance. The author's main research theme is "Understanding the mechanism underlying puberty control in aquaculturally important species." They have been actively investigating the regulatory mechanism of the BPG axis in the puberty of chub mackerel Scomber japonicus, an important fishery species. With this species, researchers can systematically collect target organs, cells, and other organs from individuals at each developmental stage, from fertilized eggs to adult fish after spawning. A highly reproducible rearing experimental system has been established, enabling verification of the knowledge gained through feedback to reared individuals. Furthermore, it has recently become possible to quickly and efficiently produce gene knockout lines using genome editing. This article introduces the mechanism of puberty control in chub mackerel by fully leveraging this experimental platform. Focus will be directed to the functions of kisspeptin, which triggers puberty by regulating GnRH secretion in mammals, and leptin, which transmits nutritional information to the reproductive axis.
Jeanne F, Pilet S, Bernay B
… +4 more, Lagadu S, Delépée R, Dufour S, Sourdaine P
Gen Comp Endocrinol
· 2025 Jun · PMID 40254036
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Hypothalamic gonadotropin-releasing hormone (GnRH) regulates the production of gonadotropins, which control reproduction. In elasmobranchs, unlike other gnathostomes, GnRH is released into the systemic circulation to sti...Hypothalamic gonadotropin-releasing hormone (GnRH) regulates the production of gonadotropins, which control reproduction. In elasmobranchs, unlike other gnathostomes, GnRH is released into the systemic circulation to stimulate gonadotrope cells located in the ventral lobe of the pituitary. The aim of this study was to investigate the potential role of systemic GnRH in the regulation of the testis in Scyliorhinus canicula. Phylogeny and synteny analyses identified three GnRHs and four GnRH receptor (ScGnRHR-I1, -IIa1, -IIa2 and -IIb2). In vitro functional hormone-receptor interactions using synthetic ScGnRHs showed that all ScGnRHs were effective at receptors, except ScGnRHRIIa2, at femtomolar to nanomolar concentrations, with lower efficiency for ScGnRH1/ScGnRHRIIb2. Real-time PCR analyses in a wide range of tissues, including male and female reproductive tracts, showed that all three gnrh were expressed mainly in the brain and all four gnrhr were expressed in the testis, particularly during spermiogenesis. Testicular explants containing cysts with spermatids were treated with ScGnRHs and their protein content analyzed by NanoLC-ESI-MS/MS, highlighting 1677 significantly differentially expressed proteins. Among them, the growth hormone receptor (GHR) and proteins involved in cholesterol and steroid metabolism, including several HSD17bs, were upregulated. In situ hybridization showed that ghr, hsd17b3 and hsd17b12 transcripts were localized in Sertoli cells, which are the main testicular steroidogenic cells in S. canicula. Fifteen steroids were assayed in the culture media, using LC-ESI-HRMS/MS, and an increase in 17β-estradiol concentrations was observed, consistent with hsd17b expressions. Furthermore, proteins involved in transcription and DNA structure were downregulated in response to GnRHs. In conclusion, this study showed that ScGnRHs may play a direct role in the regulation of elasmobranch testes by promoting spermiogenesis and modulating steroidogenesis.
Gen Comp Endocrinol
· 2025 Jun · PMID 40252850
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Gonadotropin-inhibitory hormone (GnIH) is a neuropeptide that typically acts in the hypothalamic-pituitary-gonadal (HPG) axis to regulate reproductive activity and sociosexual behaviors. GnIH is synthesized in the brain...Gonadotropin-inhibitory hormone (GnIH) is a neuropeptide that typically acts in the hypothalamic-pituitary-gonadal (HPG) axis to regulate reproductive activity and sociosexual behaviors. GnIH is synthesized in the brain and in the gonads, where it can act via its cognate receptor. However, immunohistological evidence in songbirds also shows GnIH projections towards the brainstem. We propose that GnIH can act within the spinal cord and possibly on a variety of organs to induce rapid behavioral and physiological changes in response to environmental cues. Here we used immunohistochemistry (IHC) and PCR to document GnIH and its receptor in zebra finch (Taeniopygia guttata) spinal cord. We found immunoreactive GnIH throughout the length of the spine, predominantly in the central gray matter of the cervical region. mRNA for the GnIH precursor gene and receptor gene was also present throughout the length of the spinal cord. This is the first evidence of GnIH in the avian spinal cord. These results hint at a novel pathway for neuropeptide action in vertebrates.